My broad objectives are to experimentally explore in vitro mammalian neuronal systems suitable for study of 1) physiological, pharmacological and anatomical properties of synaptic transmission, 2) mechanism of action of clinically useful drugs including anticonvulsants and anesthetics, and 3) physiological and pharmacological bases for states of altered neuronal function including epilepsy and toxic-metabolic encephalopathy. My research has involved investigation of cultured murine spinal cord and cerebellar neurons using intracellular recording techniques coupled with a) iontophoresis of drugs and putative neurotransmitters and b) anatomical study of neuronal morphology and synaptic connectivity using intracellular injection of horseradish peroxidase. Mammalian neuronal cell cultures have methodological advantages including: 1) visual placement of iontophoretic pipettes on somatic or denritic locations, 2) simultaneous intracellular recording from pairs of neurons, 3) simultaneous impalement of single neurons by two electrodes, 4) two-dimension anatomical organization, and 5) control over the extracellular medium. Initial studies have provided electrophysiological and anatomical information concerning synaptic transmission between identificable cell types as well as pharmacological properties of postsynaptic amino acid receptors, and have shown that such cultures retain much of the physiological, pharmacological and anatomical complexity present in vivo. Investigation of convulsants and anticonvulsants has suggested that postsynaptic modulation of GABA responses may underlie the mechanism of action and has suggested that cultured neurons may provide a model for study of cellular bases of epileptogenesis. The experiments poposed here are designed to extend these observations by examining the action of convulsants and anticonvulsants on presynaptic transmitter release and on the postsynaptic receptor-ionophore complex and the basis for paroxysmal activity in the spinal cord, cerebellum and forebrain cultures. It is hoped that such studies will provide insight into the cellular mechanisms underlying epilepsy as well as an extending knowledge of mammalian synaptic transmission in the central nervous system.